Naringin Attenuates the Diabetic Neuropathy in STZ-Induced Type 2 Diabetic Wistar Rats (original) (raw)
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Diabetologia, 1996
N-acetylcysteine (NAC) is a precursor of glutathione (GSH) synthesis, a free radical scavenger and an inhibitor of tumour necrosis factor (~ (TNF). Because these functions might be beneficial in diabetic complications, in this study we examined whether NAC inhibits peripheral neuropathy. Motor nerve conduction velocity (MNCV) was significantly decreased in streptozotocin-induced-diabetic Wistar rats compared to control rats. Oral administration of NAC reduced the decline of MNCV in diabetic rats. Structural analysis of the sural nerve disclosed significant reduction of fibres undergoing myelin wrinkling and inhibition of myelinated fibre atrophy in NACtreated diabetic rats. NAC treatment had no effect on blood glucose levels or on the nerve glucose, sorbitol and cAMP contents, whereas it corrected the decreased GSH levels in erythrocytes, the increased lipid peroxide levels in plasma and the increased lipopolysaccharide-induced TNF activity in sera of diabetic rats. Thus, NAC inhibited the development of functional and structural abnormalities of the peripheral nerve in streptozotocin-induced diabetic rats.
Endocrine Regulations
Objective. Diabetes induces sensory symptoms of neuropathy as positive (hyperalgesia), negative (hypoalgesia), or both. Methods. In the present study, fifty male Wistar rats were allocated to five groups: control, control+nitrate, diabetes, diabetes+insulin, and diabetes+nitrate. Thirty days after diabetes confirmation, insulin (2–4 U/day) was injected subcutaneously in diabetes+insulin group and nitrate (100 mg/l) was added into drinking water of the control+nitrate and diabetes+nitrate groups for a period of 2 months. In order to assess the mechanical and thermal algesia, tail immersion, hot plate, and von Frey tests were performed. The serum insulin levels were determined with insulin ELISA Kit. Serum level of NOx was determined by the Griess method. Results. Both thermal and mechanical nociceptive thresholds showed a significant decrease (p<0.05) which was followed by a significant increase (p<0.01) in the thermal nociceptive threshold in the diabetes group. Chronic nitrat...
2014
The objective of the present study was to investiga te the effect of concomitant administration of trig onelline (TRIG) along with sitagliptin (SITA) on glucose level, beh avior, oxidative stress and histological studies in n cotinamidestreptozotocin induced diabetic neuropathy in Wista r rats. Diabetes was induced by administration of s treptozotocin (65 mg/kg i.p), 15 min after nicotinamide (110mg/kg ) injection. After developing hyperglycemia, contro l and diabetic rats were randomly selected and divided in to five groups (n=6). These includes , Group 1 was: nondiabetic, Group 2: diabetic control, Group 3: diabetic + TRIG (50 mg/kg), Group 4: diabetic + SITA (5 mg/kg), Group 5: diabetic + TRIG (50mg/kg) + SITA (5 mg/kg). TRIG, S ITA and TRIG+SITA administered for 4 weeks. Serum glucose (SG) levels and body weights of anima ls were measured at every week of study period. Mot or nerve conduction velocity and behavioral parameters were also screened at 0, 4 th and at 8 weeks of stud...
Cells, 2021
Loganin is an iridoid glycoside with antioxidant, anti-inflammatory, glucose-lowering activities which may address the pathological mechanisms of painful diabetic neuropathy (PDN) related to inflammation, oxidative stress, and hyperglycemia. This study investigated the underlying mechanisms of action of loganin on PDN. The in vivo model of PDN was established by streptozotocin-nicotinamide (STZ-NA) induction in Sprague Dawley (SD) rats. Subsequently, loganin (5 mg/kg) was administered by daily intraperitoneal injection. High-glucose stimulated human SH-SY5Y cells co-incubated with loganin were used to mimic the in vitro model of PDN. Loganin improved PDN rats' associated pain behaviors (allodynia and hyperalgesia), insulin resistance index (HOMA-IR), and serum levels of superoxide dismutase (SOD), catalase and glutathione. Loganin also reduced pain-associated channel protein CaV3.2 and calcitonin gene-related peptide (CGRP) in the surficial spinal dorsal horn of PDN rats. Logani...
2015
Today in many countries modern medicine has displaced plants with many synthetic products but almost 30% of pharmaceutical preparations are still obtained directly or indirectly from plants. The modern era has seen some decline in use of medicinal plants and their extracts as therapeutic agent, particularly in developed countries, many of which either been discarded by the medical profession or now given in the form of isolated compound strategy of isolating the active principles from the medicinal plants and manufacturing a pharmaceutical preparation then became popular. H.G Raghavendra, G.Lakshmikanth*, N.Ravinaik, Y.Samatha
Animal model and biomarker of neuropathy in diabetic rodents
Neuropathy is the most common complication of diabetes mellitus (DM). It occurs in 60% of the patients and affects their quality of life. In the United States, diabetic neuropathy (DN) is the leading cause of diabetes-related hospital admissions and nontraumatic amputations. In order to identify new treatments of DN, it is necessary to select the precise animal model. The selected animal model of DN should exhibit the features present in human pathology. Diabetic rodents show many abnormalities that are seen in diabetic patients with neuropathy, including hyperalgesia, allodynia, slow nerve conduction velocity (NCV) and progressive sensory and sensory motor deficit.
Neuroprotective effects of Gymnema sylvestre on streptozotocin-induced diabetic neuropathy in rats
Experimental and Therapeutic Medicine, 2015
The application of traditional medicine for diabetes and associated complications, such as diabetic neuropathy (DN), has received increasing attention. The aim of the present study was to investigate the potential ameliorative effect of Gymnema sylvestre (Gs) in a rat model of DN. Diabetes was induced via a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Treatment with Gs extract (50 or 100 mg/kg/day) began two weeks following the administration of STZ and was continued for five weeks. Pain threshold behavior tests were performed subsequent to the five-week Gs treatment period. In addition, the serum levels of glucose, insulin and proinflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, were determined. Furthermore, the sciatic tissue levels of nitric oxide, thiobarbituric acid reactive substances and reduced glutathione were determined, as well as the activity levels of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. Levels of insulin-like growth factor (IGF), nerve growth factor (NGF), TNF-α, IL-1β and IL-6 were also assessed in the sciatic tissue. In addition, the sciatic nerve tissue samples were analyzed for histopathological alterations. The diabetic rats exhibited apparent reductions in the paw-withdrawal (31%; P<0.01) and tail-flick latencies (38%; P<0.05). Furthermore, the diabetic rats demonstrated an evident elevation in serum and sciatic levels of proinflammatory cytokines. Measured oxidative stress biomarkers were significantly altered in the sciatic nerve tissue of the diabetic rats. Treatment with Gs attenuated diabetes-induced modifica-tions with regard to the levels of serum glucose, insulin and proinflammatory cytokines. In the sciatic nerve tissue, the diabetes-induced alterations in IL levels and oxidative stress biomarkers were significantly improved in the Gs-treated rats. Furthermore, the reduction in the sciatic tissue expression levels of IGF and NGF was also ameliorated by Gs treatment. Histological analysis indicated that Gs corrected the sciatic tissue in the diabetic rats. Therefore, the results demonstrated that the neuroprotective effect of Gs may be associated with the inhibitory effect on the excessive activation of inflammatory molecules and oxidative stress mediators.
American Journal of Pharmacology and Toxicology, 2014
It was shown that hyperglycemia in diabetic patients is the main factor of diabetic peripheral neuropathies. Various pathways related to oxidative stress, vascular defect and defective endothelium dependent relaxation have been implicated in the development of diabetic peripheral neuropathy. A substantial number of studies have shown that antioxidant treatment are promising therapeutics that can prevent or correct reduced motor nerve conduction in diabetic rats by acting on these mechanisms. This study was designed to investigate the possible role of insulin treatment along with or without vitamin E or L-arginine on diabetic neuropathy. This goal was accessed by examining nerve conduction, parameters of oxidative stress and lipid peroxidation as well as the expression level of endothelial nitric oxide synthase in the sciatic nerve of control and streptozotocine-induced diabetic rats. Data showed that diabetic rats showed increased levels of serum glucose (382.5%) and sciatic nerve lipid peroxidation Marker (MDA, 261.6%) with a concomitant decrease in the expression of sciatic nerve eNOS mRNA as compared to control rats. The nerve conduction studies of the sciatic nerves of these rats showed decrease conduction as evident by delayed NCV (63.6%) and low Amplitude of Muscle Contraction (AMC, 36.4%). Solitary insulin treatment (but not vitamin-E or L-arginine) corrected serum glucose to control values and corrected nerve conduction parameters in the sciatic nerve. However, treating diabetic rats with different doses of vitamin E (300 mg kg −1 and 600 mg kg −1 ) significantly reduced oxidative stress by decreasing MDA and increasing GPx activity, corrected NCV by reducing the latency and improving AMC and increased eNOS mRNA expression in sciatic nerve with a more profound effect to seen with the high dose (600 mg kg −1 ). However, the maximum potent ameliorating effect of the vitamin E on these parameters was seen when administered in combination with insulin. On the other hand, L-arginine treatment alone or in combination with insulin had no effect on the oxidative stress markers nor eNOS expression but significantly and maximally improved NCV through reducing the conduction latency and increasing AMC. This study supported the notion that diabetic peripheral neuropathy is a multifactorial complication, caused by hyperglycemia, oxidative stress and vascular impairment. It is concluded that conjugate treatment with vitamin-E, especially in higher doses, with insulin could be of great value. Moreover correction of impaired nerve blood flow by drugs that induce nitric oxide has proved to be efficient in the protection against and correction of experimental diabetic peripheral neuropathy.
General Physiology and Biophysics, 2010
Hyperglycaemia-induced oxidative stress makes an important contribution to the aetiology of diabetic neuropathy. The aim of our study was to evaluate the effect of the antioxidant stobadine (STB) in comparison with a treatment by a high-dose of α-lipoic acid (ALA), on the neurological consequences of chronic hyperglycaemia in an animal model of diabetes in Wistar rats (16 weeks old), made diabetic by streptozotocin (STZ 3 × 20 mg i.v.). Neuropathy was evaluated electrophysiologically by measuring motor nerve conduction velocity (NCV) in the 4 th and 8 th week in vivo and motor NCV and resistance to ischaemic conduction failure (RICF) of the sciatic nerve in the 10 th week of the experiment in vitro. The therapy with ALA (100 mg/kg i.p., 5 times a week) and STB (25 mg/kg i.p., 5 times a week) had a significant effect on NCV in vivo in the 8 th week of the experiment and no effect in the 10 th week in vitro. The RICF elevated in diabetic animals was significantly modified by ALA. The effect of the antioxidant STB on NCV was comparable with that of ALA, while RICF was affected only by ALA. We conclude that treatment with appropriate antioxidants might partially prevent nerve dysfunction in diabetic rats.